Drug compositions come in many different forms and may be administered to a patient via several different routes, such as oral, parenteral, topical, intravenous, subcutaneous, intranasal, etc. Depending on the active and the treatment desired, different routes of administration may be preferable.
Some diseases and conditions may be long lasting, requiring treatment for many weeks, months, or even years. Typically, a patient taking a traditional oral dosage form (e.g., tablets or capsules) may be required to take the oral dose at least once per day for the duration of the treatment. For example, a patient may need to take an oral dose twice a day for a year or longer. The problem with treatments that require continuous dosage over a long period of time is that often the patient may not be compliant in taking the medications. In other words, the patient may forget, believe the treatment is unnecessary, or grow tired of having to take many pills over an extremely long period of time. Accordingly, treatments are necessary which can alleviate these compliance issues, but still provide effective and efficient treatment to the patient.
Tizanidine is an imidazoline central α2-adrenoceptor agonist that is effective at managing spasticity, which is an involuntary tension, stiffening or contraction of muscles. Spasticity is typically associated with conditions such as multiple sclerosis (MS), cerebral palsy, stroke, or brain or spinal cord injury. It is estimated that spasticity affects 500,000 people in the United States and 12 million people worldwide. Tizanidine is in a class of medications called skeletal muscle relaxants, and works by slowing action in the brain and nervous system to allow muscles to relax. Treatment of spasticity typically lasts many years. Many of the oral dosage forms of tizanidine that are currently on the market (e.g., Zanaflex®) are short-acting. Because of the short duration of effect, a patient must take a pill or capsule several times per day if relief from spasticity is needed throughout the day.
Currently, the only treatments for spasticity which do not involve oral dosage forms are localized botox injections, or an implantable drug pump which delivers drug intrathecally. Each of these treatments involve significant risk to the patient, and do not provide long-term relief. For example, botox injections can produce side effects such as headache, bruising, flu-like symptoms, nausea, and temporary pain and redness at the injection site. Moreover, the long term effects of multiple botox injections are not known. Implanting a drug pump involves major surgery to insert the large (e.g., hockey puck sized) pump and reservoir along with its catheter, which is connected to the spinal cord so that drug can be pumped into the spinal fluid. In addition to the risks of major surgery involving the spinal cord, the pump needs to be refilled frequently.
Accordingly, there has remained a need for effective dosage forms that provide therapeutically effective amounts of drugs that treat spasticity at relatively constant rates over a long period of time.